The long-term goal is to understand the mechanism of catalysis by catalytic antibodies (abzymes). Many reactions differing in complexity and importance have now been catalyzed. The question of whether antibodies use the same or different mechanisms, kinetics, rate enhancement steps or similar reaction profiles as enzymes can be addressed by the study of their three-dimensional structure. Our goal is to determine the X-ray structures of various catalytic Fabs in the presence and absence of their substrate or transition state analogues. It is our intent to understand the role of desolvation, acid-base catalysis, strain, proximity effects and stabilization of transition states in their catalytic mechanism. The question of how to redesign and improve abzymes by site-directed mutagenesis, introduction of functional groups such as cofactors, metals and unnatural amino acids, or by alteration of substrate or transition state design will be addressed in conjunction with the X-ray structural studies. The immediate objectives are to understand the following reactions. 1. Antibody Catalysis of a Claisen Rearrangement 2. Antibody Catalysis of a Diels-Alder Cylcoaddition 3. Antibody Catalysis of a Decarboxylation 4. Antibody Catalysis of an Amide/Ester Hydrolysis 5. Antibody Catalysis of a Transesterification Reaction 6. Antibody Catalysis of Disfavored Transformations 7. Evolution of Antibody Catalysis 8. Antibody Catalysis of Other Transformations The methods used to determine the X-ray structures will be conventional molecular replacement and standard refinement protocols. The design of stable ligands and the use of cryocrystallography will be used to collect high resolution data on relevant complexes.